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Vaia Florou, Christopher Nevala-Plagemann, Jonathan Whisenant, Patricia Maeda, Glynn W. Gilcrease, and Ignacio Garrido-Laguna

NTRK gene fusions are found in <1% of all cancers but are uniformly present in mammary analog secretory carcinomas (MASC) of the salivary glands. Two selective histology-agnostic tropomyosin receptor kinase (TRK) inhibitors are currently approved for malignancies with these oncogenic fusions. Resistance to TRK inhibition has been recognized, and the mediating mechanisms are presently being studied. This report describes a patient diagnosed with an MASC of the parotid gland who after undergoing multiple lines of treatment was found to have an ETV6-NTRK3 fusion and initiated TRK-targeted therapy using entrectinib. Upon disease progression, we performed tumor genetic sequencing that showed a secondary resistance mutation. The patient subsequently responded to selitrectinib, a next-generation TRK inhibitor.